NASA urged to lay plans for mission to Europa.
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LINE-1 (L1) retrotransposition is common in human cancers and rearrangements at insertion sites can contribute to cancer-driving oncogene amplifications and promote genome instability. However, the mechanisms underlying rearrangements of L1 retrotransposition intermediates are poorly understood. To address this gap, we developed GFP-based recombination reporter assays to study the formation of L1 retrotransposition-mediated rearrangements. Using these reporters combined with long-read sequencing, we find that L1 retrotransposition cDNA intermediates can recombine with distal DNA breaks to generate chromosomal rearrangements. We also find that two independent L1 insertion cDNA intermediates on distinct genomic loci can recombine with each other to generate chromosomal rearrangements. Both types of rearrangements depend on L1-encoded ORF2p endonuclease and reverse transcriptase activities. Using these reporters, we discover that L1 retrotransposition-mediated rearrangements are robustly induced when the recombining sequences share extensive homology and that their formation requires the homologous recombination factor BRCA1. In contrast, we find L1 retrotransposition-mediated rearrangements are suppressed by the mismatch repair factor MSH2 when the recombining sequences contain mismatches. Given the repetitive nature of our genome, these findings highlight the risk of L1 insertion intermediates becoming substrates for aberrant recombination and promoting genome instability.
The purpose of this study was to determine whether the Hearing Handicap Inventory for the Elderly (HHIE) screening version translated into Chinese can be used as a valid screening instrument for the identification of hearing impairment in Chinese-speaking elderly persons. One hundred elderly Chinese Americans were screened, and the majority of the subjects did not report hearing handicap. A comparison among different screening protocols (ASHA, 40 dB HL at 1000 and 2000 Hz; HHIE-S > 10 and HHIE-S > 10 and 40 dB HL at 1 and 2 kHz) suggested that the combined HHIE-S and 40 dB HL cutoff at 1000 and 2000 Hz achieved the best referral rates. Some hypotheses explaining the results are discussed relative to cultural and linguistic differences between elderly Chinese Americans and their white English-speaking counterparts.
A case of spontaneous staphylococcus arthritis of the wrist with associated carpal and distal radius osteomyelitis is reported. Following sequential debridements and a 6-week course of parenteral antibiotics, an extensive defect was bridged with a vascularized fibular autograft to achieve a successful fusion. There was no donor site morbidity or recurrent infection. Follow-up radiographs 41 months later demonstrated complete incorporation and hypertrophy of the graft.
We describe the technique of wire-loop fixation to treat 4 young men with a unique variant of Melone's type 4 articular fracture of the volar lunate facet, characterized by a displaced rotated articular fragment supported by a limited amount of subchondral bone. This is an unusual injury that threatens the integrity of both the radiocarpal and distal radioulnar joints. It is the result of a compressive force to the wrist and may require trispiral computed tomography for delineation. Open reduction and internal fixation is recommended to maintain stability and articular congruity. The displaced volar-articular fragment, however, may be relatively small; therefore, direct manipulation could lead to soft tissue stripping and osteonecrosis. We have found the technique of wire-loop fixation to be a simple, reproducible, and effective alternative method of internal fixation for these difficult fractures. Malunion, nonunion, loss of fixation, tendon rupture, infection, arthrosis, or pain caused by hardware has not occurred. Use of this technique is not recommended in patients with osteoporotic bone.
We report the morphology and treatment of 2 cases of a triplane intra-articular bicondylar fracture of the head of the proximal phalanx. Fracture lines in the coronal, sagittal, and transverse planes characterize this fracture, making it highly unstable. Open reduction and internal fixation using two 1.5-mm interfragmentary screws oriented in a dorsal to volar direction resulted in anatomic restoration of the articular surfaces and satisfactory functional results. In 1 case, autogenous cancellous bone graft was harvested from the ipsilateral radial styloid to support the articular fragments.
Ten patients with malaligned fractures of the distal radius that demonstrated either delayed healing or the development of an atrophic or synovial nonunion on standard radiographs were treated with surgical realignment, stable internal fixation, and autogenous iliac crest bone grafting. All 10 fractures healed with acceptable radiologic alignment within 3 months of the index procedure. After an average follow-up period of 3 years 6 months (range, 2 years to 8 years 6 months) patients had an average of 105 degrees wrist flexion and extension, 145 degrees forearm rotation, and 73% grip strength compared with the opposite limb. In the treatment of malaligned, ununited fractures of the distal radius, specific techniques and implants must be tailored to the deformity of the distal radius and the shape of the distal fragment. A stable, well-aligned wrist with preservation of at least 50 degrees mobility in flexion and extension was achieved in every patient, but the final result was compromised by associated problems in 3 patients.
The purpose of this study was to evaluate the mechanical properties of a bioresorbable plate and screw system that was developed for the treatment of unstable metacarpal fractures and to compare the strength and stiffness of this system with those of conventional titanium plates and screws. Using a 4-point bending test, we measured the strength and stiffness of these implants over a 12-week period of in vitro degradation. Our data suggest that these implants provide stable bending strength and stiffness for 8 weeks and gradually lose their strength over a period of 12 weeks. Further research is necessary to determine whether this level of fixation is adequate to stabilize unstable metacarpal fractures.
Secondary ulnar nerve palsy, an unusual condition in which the onset of ulnar nerve dysfunction occurs 1 to 3 months after elbow trauma, can be the cause of sudden deterioration of elbow function. Initially recognized in 1899, this condition has not been reported often. We describe 2 patients who had no subjective or objective evidence of ulnar nerve dysfunction after elbow trauma but had a sudden loss of motion, pain, and clinical and electrophysiologic evidence of ulnar nerve compression at the elbow 4 to 5 weeks after trauma. Marked improvement occurred after ulnar nerve subcutaneous transposition and contracture release.
Two cohorts of 10 patients who had a corrective osteotomy for a malunited fracture of the distal radius with a pi-shaped plate and screw fixation were compared retrospectively to see whether the outcome was affected by using a nonstructural cancellous bone graft compared with a trapezoidal corticocancellous bone graft. The indications for the osteotomy, surgical techniques, and postoperative rehabilitation were consistent and all surgical procedures were done by the same surgeon. All osteotomies healed without loss of the surgical correction. Follow-up radiographic and functional results were comparable between groups. Use of a nonstructural, cancellous only bone graft-appealing in its relative simplicity-seems safe and efficacious.
Twenty patients aged 60 years or older (average age, 68 y) presented to our institution with a distal radius fracture made complex by virtue of displacement after a closed reduction and cast or external fixation immobilization. Ten of the fractures were volarly angulated and 10 were dorsally angulated. Fifteen patients' hands had associated soft-tissue swelling. Surgical exposure and stable internal fixation were undertaken to both realign the fracture as well as enable functional rehabilitation. The final functional result and radiographic results were physician rated and patient rated by using the Patient Rated Wrist Evaluation (PRWE). The patients' overall activity level was quantified and compared with population norms by using the Physical Activity Scale for the Elderly (PASE). At an average follow-up visit of 38 months, all the fractures healed and none of the implants loosened or broke. The functional results were excellent in 7, good in 11, and fair in 2. The average PRWE score was 14, which compares favorably with prior studies of adult patients of all ages treated for a distal radius fracture. The PASE score averaged 177, representing a return to preoperative activity levels in 17 of 20 patients. Complications included loss of alignment, tendon rupture, transient radial sensory neuritis, and nonfatal pulmonary embolism in 1 patient each. Six plates were removed because of soft-tissue irritation.
Stable internal fixation is essential to obtain healing of an ununited fracture of the proximal humerus. Standard plate and screw fixation may be inadequate to secure a small, osteopenic proximal fragment. We used blade plates and autogenous cancellous bone graft to repair ununited fractures of the proximal humerus in 25 patients (19 women and 6 men) with a mean age of 61 years. Healing was documented in 23 of 25 patients (92%). Objective and subjective instruments documented substantial functional improvement in patients with healed fractures. The results were classified as good or excellent in 20 of 25 patients, and few complications were encountered. Blade plate fixation facilitates successful treatment of ununited fractures of the proximal humerus.
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As the field of astrobiology matures and search strategies for life on other worlds are developed, the need to analyze in a systematic way the plausibility for life on other planetary systems becomes increasingly apparent. We propose the adoption of a simple plausibility of life (POL) rating system based on specific criteria. Category I applies to any body shown to have conditions essentially equivalent to those on Earth. Category II applies to bodies for which there is evidence of liquid water and sources of energy and where organic compounds have been detected or can reasonably be inferred (Mars, Europa). Category III applies to worlds where conditions are physically extreme but possibly capable of supporting exotic forms of life unknown on Earth (Titan, Triton). Category IV applies to bodies that could have seen the origin of life prior to the development of conditions so harsh as to make its perseverance at present unlikely but conceivable in isolated habitats (Venus, Io). Category V would be reserved for sites where conditions are so unfavorable for life by any reasonable definition that its origin or persistence there cannot be rated a realistic probability (the Sun, gas giant planets). The proposed system is intended to be generic. It assumes that life is based on polymeric chemistry occurring in a liquid medium with uptake and degradation of energy from the environment. Without any additional specific assumptions about the nature of life, the POL system is universally applicable.
If Europa is to be of primary exobiological interest, namely, as a habitat for extant life, it is obvious that (a) a hydrosphere must prevail beneath the cryosphere for a long time, (b) internal energy sources must be present in a sufficient state of activity, and (c) a reasonable technical means must be available for assessing if indeed life does exist in the hypothesized hydrosphere. This discussion focuses on the last point, namely, technological issues, because the trend of the compounding evidence about Europa indicates that the first two points are likely to be true. First, we present a consideration of time-of-flight mass spectroscopy conducted in situ on the cryosphere surface of Europa during a first landed robotic mission. We assert that this is a reasonable technical means not only for exploring the composition of the cryosphere itself, but also for locating any biomolecular indicators of extant life brought to the surface through cryosphere activity. Secondly, this work also addresses practical issues inherent in any kind of instrumental interrogation of a surface whose properties are governed by radiation chemistry. This includes advocating the construction of a Europan surface simulator to familiarize instrumental system developers with the spacecraft- and instrument-scale conditions under which such an interrogation would take place on Europa. Such a simulator is mandatory in certification of the functional utility of a flight instrument.
Liquid water, as far as we know, is an indispensable ingredient of life. Therefore, locating reservoirs of liquid water in extraterrestrial bodies is a necessary prerequisite to searching for life. Recent geological and geophysical observations from the Galileo spacecraft, though not unambiguous, hint at the possibility of a subsurface ocean in the Jovian moon Europa. After summarizing present evidence for liquid water in Europa, we show that electromagnetic and seismic observations made from as few as two surface observatories comprising a magnetometer and a seismometer offer the best hope of unambiguous characterization of the three-dimensional structure of the ocean and the deeper interior of this icy moon. The observatories would also help us infer the composition of the icy crust and the ocean water.
While Europa has emerged as a leading candidate for harboring extraterrestrial life, the apparent lack of a source of free energy for sustaining living systems has been argued. In this theoretical analysis, we have quantified the amount of energy that could in principle be obtained from chemical cycling, heat, osmotic gradients, kinetic motion, magnetic fields, and gravity in Europa's subsurface ocean. Using reasonable assumptions based on known organisms on Earth, our calculations suggest that chemical oxidation-reduction cycles in Europa's subsurface ocean could support life. Osmotic and thermal gradients, as well as the kinetic energy of convection currents, also represent plausible alternative sources of energy for living systems at Europa. Organisms thriving on these gradients could interact with each other to form the complex energy cycling necessary for establishing a stable ecosystem.